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1.
Arch Gynecol Obstet ; 301(2): 591-602, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31853712

RESUMO

PURPOSE: With better access to early diagnosis and appropriate treatment, cervical cancer (CC) burden decreased in several European countries. In Eastern European (EE) countries, which accessed European Union in 2004, CC survival was worse than in the rest of Europe. The present study investigates CC survival differences across five European regions, considering stage at diagnosis (local, regional and metastatic), morphology (mainly squamous versus glandular tumours) and patients' age. METHODS: We analysed 101,714 CC women diagnosed in 2000-2007 and followed-up to December 2008. Age-standardised 5-year relative survival (RS) and the excess risks of cancer death in the 5 years after diagnosis were computed. RESULTS: EE women were older and less commonly diagnosed with glandular tumours. Proportions of local stage cancers were similar across Europe, while morphology- and stage-specific RS (especially for non-metastatic disease) were lower in Eastern Europe. Adjusting for age and morphology, excess risk of local stage CC death for EE patients remained higher than that for other European women. CONCLUSION: Stage, age and morphology alone do not explain worse survival in Eastern Europe: less effective care may play a role, probably partly due to fewer or inadequate resources being allocated to health care in this area, compared to the rest of Europe.

2.
Adv Clin Exp Med ; 28(10): 1377-1383, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31638746

RESUMO

BACKGROUND: Poland is considered among the European countries with an average incidence of cervical cancer (CC; about 3,000-3,500/year) and at the same time with high mortality (5-year survival rate - 55.2%). For this reason, in 2006 Poland introduced a Population-Based Cervical Cancer Prevention and Early Detection Program addressed to women aged 25-59 years, in which a cytological test is carried out every 3 years. OBJECTIVES: The aim of the study was to assess the changes in the curability of CC patients brought by the introduction of the Screening Program in the Lower Silesian voivodeship and to identify the subpopulation of women for whom activities aimed at increasing adherence rates must be intensified. MATERIAL AND METHODS: The 5-year relative survival in 3,586 CC patients from 2000-2010 registered in the Lower Silesian Cancer Registry was analyzed. RESULTS: In the Lower Silesian voivodeship, a 55.1% 5-year survival rate was recorded in 2000-2004 and 70.5% in 2010. The highest increase in 5-year relative survival rates was found in rural communities (from 53.1% in 2000-2004 to 77.7% in 2010) and in Wroclaw (56.8% and 74.2%, respectively). In the study group, the number of patients with invasive CC (C53) detected in the local stage of the disease increased systematically from 61.5% in 2000-2004 to 74.3% in 2010. CONCLUSIONS: The introduction of the population-based screening program improved the curability rate in CC patients in the Lower Silesian voivodeship. In order to maintain the recent positive trends, further education should be continued, and activities aimed at increasing adherence to screening tests should be intensified, especially in urban-rural communities.


Assuntos
Programas de Rastreamento/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Cooperação do Paciente/estatística & dados numéricos , Neoplasias do Colo do Útero/diagnóstico , Adulto , Detecção Precoce de Câncer , Feminino , Humanos , Incidência , Masculino , Programas de Rastreamento/organização & administração , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Cooperação do Paciente/psicologia , Polônia/epidemiologia , Vigilância da População , Avaliação de Programas e Projetos de Saúde , Taxa de Sobrevida/tendências , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
3.
Oncol Lett ; 18(4): 3561-3570, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31579068

RESUMO

Classic prognostic factors, such as clinical advancement of the disease and histological grade of the tumor, continue to have a decisive role in the selection of therapeutic strategy in patients with carcinoma of the oral cavity floor and oral surface of the tongue (OCC). YAP1/Yes-associated protein 1 (YAP) and transcriptional co-activator with PDZ-binding motif, WWTR1 (TAZ) proteins, appear to be promising markers that may be used to develop personalized therapies. The aim of the present study was to analyze the associations between the levels of YAP, TAZ and tyrosine-protein phosphatase non-receptor type 14 (PTPN14) and to determine whether the increased expression of YAP and TAZ had an effect on tumor cell proliferation, as determined by minichromosome maintenance 7, DNA replication licensing factor 7 expression. Their prognostic value was also assessed. In total, 127 patients who underwent radical surgery and were subjected to adjuvant radiation therapy due to squamous cell OCC were enrolled in the present study. The results demonstrated an evident effect as YAP expression increased in cancer-associated fibroblasts, which induced unfavorable prognosis in patients. In addition, a positive association between proliferation in cancer cells and YAP expression in stromal cells was observed. A lack of YAP expression in the cytoplasm of tumor cells was a factor for poor prognosis with regard to disease-free survival and disease specific survival. No statistically significant correlations between YAP and TAZ expression and PTPN14 expression were identified, nor was a correlation between cell proliferation and the presence of YAP and TAZ in tumor cells observed. The results indicated that YAP expression levels may support the development of personalized therapies for patients.

4.
Rep Pract Oncol Radiother ; 24(4): 325-330, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31193916

RESUMO

Aim: The aim of the analysis was to compare doses obtained for temporal lobes in patients being irradiated for meningiomas of the brain using the conformal technique and volumetric modulated arc therapy (VMAT). We try to answer the question whether the application of VMAT would lead to higher doses within temporal lobes. Background: In recent years a significant increase in the detection of meningiomas and effectiveness of treatment has been observed. Hence quality of life should be considered as an important aspect after a treatment course. Materials and methods: Treatment plans of 27 patients were evaluated retrospectively. Radiotherapy procedures were carried out from 2007 until 2016 at the Department of Radiation Oncology in Wroclaw, Poland. For individual patients, alternative treatment plans were generated in relation to the ones originally used, wherein from dynamic techniques, volumetric modulated arc therapy was selected for analysis. Evaluated dosimetric parameters for temporal lobes were: mean dose, V10 Gy, V20 Gy, V45 Gy. Results: Statistically significant differences were observed for V45 Gy for both temporal lobes (p = 0.023) and for V45 Gy for the right (p = 0.001) and the left temporal lobe (p = 0.016) considered for VMAT. The mean values of the V45 Gy for both temporal lobes, for the right temporal lobe and for the left temporal lobe were lower for VMAT than for 3D, respectively: 7.54% and 7.90%, 6.82% and 9.47%, 5.67% and 7.14%.Analysis of the remaining results found no statistical differences. Conclusion: Application of VMAT in patients treated for meningioma of the brain is not related to higher doses of radiation in the temporal lobe area, compared with the conformal technique.

5.
Onco Targets Ther ; 11: 1413-1422, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29559799

RESUMO

Background: FOXP1 is a pleiotropic protein that plays important roles in immune responses (B-cell development regulation and differentiation of monocyte), organ development (cardiac valves, lung, and esophagus), and neuronal development. Besides being the primary regulator of normal human tissue development, FOXP1 also plays a role in tumorigenesis. However, the potential value of FOXP1 expression in tumor prognosis remains controversial. FOXP1 expression was assessed in tumor cells (TCs) and stromal cells (SCs) of cutaneous melanomas with the aim of analyzing the associations between FOXP1 expression and clinicopathological characteristics. We believe this article to be the first report analyzing the correlations between FOXP1 expression and clinicopathological, as well as histological, characteristics in melanoma. Materials and methods: In total, 96 formalin-fixed, paraffin-embedded primary cutaneous melanoma tissue specimens were subjected to immunohistochemical analysis for FOXP1, and the results were correlated with classical clinicopathological features and patient survival. Results: FOXP1 overexpression in TCs was strongly associated with the presence of metastases in sentinel lymph nodes (p=0.0003, OR=11.66) and positive status of regional lymph nodes (p=0.0006, OR=22.15). In 96% (52 of 54) of patients presenting with low FOXP1 expression, no clinical or histopathological features of lymphatic dissemination were observed. However, thinner and nonulcerated tumors were reported to have increased numbers of FOXP1-positive SCs. In addition, a strong association was observed between FOXP1 upregulation in SCs and the absence of regional lymph node metastases. There was a significant correlation between FOXP1 upregulation in TCs and shorter cancer-specific overall survival (log-rank test, p=0.0040) and disease-free survival (log-rank test, p=0.0021). FOXP1 expression was confirmed in multivariate analysis as a factor that significantly unfavorably impacts prognosis in melanoma patients (HR=3.14, p=0.0299, adjusted for age, Breslow thickness, and sex). Conclusion: The findings from this study indicate that FOXP1 has a major role in melanoma progression, which makes it a candidate for molecular target-based cancer therapy.

6.
Diagn Pathol ; 12(1): 88, 2017 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-29284501

RESUMO

BACKGROUND: The nucleolus is an organelle that is an ultrastructural element of the cell nucleus observed in H&E staining as a roundish body stained with eosin due to its high protein content. Changes in the nucleoli cytomorphology were one of the first histopathological characteristics of malignant tumors. The aim of this study was to assess the relationship between the cytomorphological characteristics of nucleoli and detailed clinicopathological parameters of melanoma patients. Moreover, we analyzed the correlation between cytomorphological parameters of nucleoli and immunoreactivity of selected proteins responsible for, among others, regulation of epithelial-mesenchymal transition (SPARC, N-cadherin), cell adhesion and motility (ALCAM, ADAM-10), mitotic divisions (PLK1), cellular survival (FOXP1) and the functioning of Golgi apparatus (GOLPH3, GP73). METHODS: Three characteristics of nucleoli - presence, size and number - of cancer cells were assessed in H&E-stained slides of 96 formalin-fixed paraffin-embedded primary cutaneous melanoma tissue specimens. The results were correlated with classical clinicopathological features and patient survival. Immunohistochemical analysis of the above mentioned proteins was described in details in previous studies. RESULTS: Higher prevalence and size of nucleoli were associated with thicker and mitogenic tumors. All three nucleolar characteristics were related to the presence of ulceration. Moreover, microsatellitosis was strongly correlated with the presence of macronucleoli and polynucleolization (presence of two or more nucleoli). Lack of immunologic response manifested as no TILs in primary tumor was associated with high prevalence of melanoma cells with distinct nucleoli. Interestingly, in nodular melanoma a higher percentage of melanoma cells with prominent nucleoli was observed. In Kaplan-Meier analysis, increased prevalence and amount, but not size of nucleoli, were connected with shorter cancer-specific and disease-free survival. CONCLUSION: (1) High representation of cancer cells with distinct nucleoli, greater size and number of nucleoli per cell are characteristics of aggressive phenotype of melanoma; (2) higher prevalence and size of nucleoli are potential measures of cell kinetics that are strictly correlated with high mitotic rate; and (3) high prevalence of cancer cells with distinct nucleoli and presence of melanocytes with multiple nucleoli are features associated with unfavorable prognosis in patients with cutaneous melanoma.


Assuntos
Nucléolo Celular/patologia , Melanoma/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Prognóstico , Neoplasias Cutâneas/mortalidade , Adulto Jovem
7.
World J Surg Oncol ; 14: 72, 2016 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-26956623

RESUMO

BACKGROUND: The aim of this study was to assess the usefulness of the breast segmentectomy with rotation mammoplasty (BSRMP) in conserving therapy for an extensive ductal carcinoma in situ (DCIS) with or without an invasive component. METHODS: Thirty-six women with DCIS visible as large area of microcalcifications distributed out of the retroareolar area regardless of the quadrant were studied prospectively. All the patients underwent BSRMP and axillary procedure (31 sentinel node biopsy, 5 axillary dissection) followed by radiotherapy. In each case, follow-up was carried out carefully and special effort was made to identify postoperative complications. Cosmetic result was judged 6 months after radiotherapy by the patient herself and two surgeons being rated as poor, mediocre, medium, good or excellent. RESULTS: Operation was completed without any difficulties in all the cases. Appropriate BSRMP was easily done after the skin marking. Regardless of the type of axillary approach, it was conveniently performed. Wound was healed by primary adhesion; skin or breast tissue necrosis did not develop. Neither haematoma nor surgical site infection was observed. In none of the patient, centralisation of the nipple-areola complex (NAC) was needed. Three patients (8.3%) with close margins (1 mm or less) successfully underwent subsequent re-excision. The scar did not result in any impairment of arm movement. Cosmetic outcome was evaluated by the women as excellent and good in 55 (87%) and 8 (13%) cases, respectively, while by the surgeons as excellent, good and medium in 52 (82%), 8 (13%), and 3 cases (5%), respectively. CONCLUSIONS: BSRMP is a simple and safe technique achieving good cosmetic results without NAC centralisation and giving the wide and easy access to axilla for both sentinel node biopsy and lymphadenectomy. It can be helpful in cases of extensive, radially spreading tumours (in particular DCIS or invasive cancers with intraductal component), eccentric lesions, or superficially located cancers when the neighbouring skin is excised. However, due to its limitations (long incision, difficult subsequent mastectomy, possibility of scar placement in the visible area of decollete), a careful patients' selection should be done. Further studies are needed to assess long-term cosmetic outcomes including delayed post-radiotherapy effects.


Assuntos
Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Mamoplastia/métodos , Mastectomia Segmentar/métodos , Complicações Pós-Operatórias , Adulto , Idoso , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Rotação
8.
Rep Pract Oncol Radiother ; 19(6): 353-60, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25337407

RESUMO

This survey is performed to update knowledge about methods and trends in lung cancer radiotherapy. A significant development has been noticed in radiotherapeutic techniques, but also in the identification of clinical prognostic factors. The improvement in the therapeutic line includes: application of the four-dimensional computer tomography (4DCT), taking advantage of positron emission tomography (PET-CT), designing of new computational algorithms, allowing more precise irradiation planning, development of treatment precision verification systems and introducing IMRT techniques in chest radiotherapy. The treatment outcomes have improved with high dose radiotherapy, but other fractionation alternations have been investigated as well.

9.
Head Neck ; 36(3): 419-24, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23729003

RESUMO

BACKGROUND: The purpose of our study was to evaluate if DNA methylation level in leukocytes may be used as a surrogate marker of genome methylation status in laryngeal cancer tissues. METHODS: We evaluated global DNA methylation using an ultra performance liquid chromatography (UPLC)-based method to assess the total content of 5-methylcytosine (5 mC). RESULTS: The study was performed on DNA isolated from cancer tissues, adjacent normal tissues, and peripheral blood leukocytes in a group of 72 patients with laryngeal cancer. DNA hypomethylation was found in tumor tissue (56%) and normal tissue (49%). There was a significant correlation between the levels of 5 mC in these 2 types of tissue. There was no significant DNA hypomethylation in blood. A negative correlation between tumor grade and blood levels of 5 mC was found. CONCLUSION: The level of leukocyte DNA methylation measured using total 5 mC content cannot be used as a surrogate marker for genome methylation status in laryngeal cancer tissues.


Assuntos
Metilação de DNA , Neoplasias Laríngeas/metabolismo , 5-Metilcitosina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Cromatografia Líquida , Epigenômica , Feminino , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-Idade
10.
Ginekol Pol ; 84(7): 590-5, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24032269

RESUMO

INTRODUCTION: Due to frequent diagnosis of ovarian cancer at an advanced clinical stage, in most cases surgical debulking is followed by chemotherapy. The principal cause of therapeutic failure involves incomplete surgery and resistance of neoplastic cells to chemotherapy. A search continues for substances which would overcome resistance to treatment and, as a result, would increase efficacy of the applied treatment. Quercetin represents one of more interesting compounds, which at present in subjected to several tests. MATERIAL AND METHODS: Studies were performed on in vitro sensitivity of human ovarian cancer cell lines, SKOV-3, EFO27, OVCAR-3 and A278OP to low doses of quercetin and on the effect exerted by quercetin on sensitivity of the cell lines to cisplatin and pactitaxel. RESULTS: The experiments proved that the studied cells of ovarian cancer manifest a similar sensitivity to quercetin. Following incubation of the cells with two distinct concentrations of quercetin and the studied cytostatic agents all the cells lines were found to significantly increase their sensitivity to pactitaxel in cases of two cell lines, OVCAR-2 and A278OP, they also significantly increased their sensitivity to cisplatin. DISCUSSION: Our results demonstrated suitability of low quercetin doses (achievable using oral administration) as a substance which increases sensitivity of ovarian cancer cells to cisplatin and paclitaxel. The value of quercetin include its wide accessibility efficacy and a broad range of activity but also its low toxicity as compared to other examined compounds. CONCLUSIONS: Used in low doses, quercetin increases chemosensitivity of ovarian cancer cells examined compounds.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Antioxidantes/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Ovarianas/tratamento farmacológico , Quercetina/farmacologia , Apoptose/efeitos dos fármacos , Sobrevivência Celular , Cisplatino/farmacologia , Feminino , Humanos , Paclitaxel/farmacologia , Células Tumorais Cultivadas
11.
Radiother Oncol ; 107(2): 171-7, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23590986

RESUMO

PURPOSE: To present an interim analysis of the trial comparing two neoadjuvant therapies for unresectable rectal cancer. METHODS: Patients with fixed cT3 or cT4 or locally recurrent rectal cancer without distant metastases were randomized to either 5 × 5 Gy and 3 courses of FOLFOX4 (schedule I) or 50.4 Gy delivered in 28 fractions given simultaneously with 5-Fu, leucovorin and oxaliplatin (schedule II). Surgery in both groups was performed 12 weeks after the beginning of radiation and 6 weeks after neoadjuvant treatment. RESULTS: 49 patients were treated according to schedule I and 48 according to schedule II. Grade III+ acute toxicity was observed in 26% of patients in group I and in 25% in group II. There were two toxic deaths, both in group II. The microscopically radical resection (primary endpoint) rate was 73% in group I and 71% in group II. Overall and severe postoperative complications were recorded in 27% and 9% of patients vs. 16% and 7%, respectively. Pathological complete response was observed in 21% of the patients in group I and in 9% in group II. CONCLUSIONS: The interim analysis revealed no major differences in acute toxicity and local efficacy between the two evaluated strategies.


Assuntos
Terapia Neoadjuvante , Neoplasias Retais/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/efeitos adversos , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Neoplasias Retais/patologia
12.
Adv Clin Exp Med ; 22(1): 5-15, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23468257

RESUMO

For many years, the age of the patient, the condition of axillar lymph nodes, the size of the tumour, histological traits (in particular histological grade of malignancy and invasion of lymphatic vessels), condition of hormonal receptors and HER2 represented principal factors used for the stratification of breast cancer patients for the purposes of evaluating the prognosis and determining the appropriate strategy of treatment. Although the variables are useful for the prognostic evaluation of individual groups of breast cancer patients, their role in determining the individual risk level of the patient and in the selection of supplementary treatment is quite restricted. This article shows the prognostic value of additional parameters, whose expression is associated with chemioresistance (MRP2, BCRP, YB1) or individual assessment of the dynamics of tumor progression (S100P, BUBR1). In addition, it describes the role of an online database of "The Kaplan-Meier plotter" which contains the assessment of the effects of expression of various genes on the clinical outcome of patients with breast cancer.


Assuntos
Neoplasias da Mama/diagnóstico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/classificação , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Citostáticos/farmacologia , Citostáticos/uso terapêutico , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Prognóstico
13.
Histol Histopathol ; 28(4): 513-24, 2013 04.
Artigo em Inglês | MEDLINE | ID: mdl-23364898

RESUMO

S100P - low molecular weight acidic protein has been shown to be involved in processes of proliferation, survival, angiogenesis, multidrug resistance and metastasis in various human malignancies. In breast cancer, S100P expression is associated with immortalization of neoplastic cells and aggressive tumour behaviour, indicating that this protein may have adverse prognostic value. We analyzed nuclear and cytoplasmic expression of S100P in 85 stage II breast cancer patients with a median follow up of 17 years. Immunohistochemical reactions were performed on paraffin sections of primary tumours, using monoclonal antibodies against S100P. We also studied prognostic value of S100P mRNA expression using the KM plotter which assessed the effect of 22,277 genes on survival in 2422 breast cancer patients. Moreover, the relationship was examined between expression of S100P in cells of four breast cancer cell lines and their sensitivity to the 11 most frequently applied cytotoxic drugs. Univariate and multivariate analyses showed that higher expression of nuclear S100P (S100Pn) was typical for cases of a shorter overall survival and disease-free time. KM plotter analysis showed that elevated S100P expression was specific for cases of a relapse-free survival and distant metastases-free survival. No relationship could be documented between expression of S100P and sensitivity of breast cancer cells to cytostatic drugs. We demonstrated that a high S100Pn expression level was associated with poor survival in early stage breast cancer patients. Since preliminary data indicated that expression of S100P was up-regulated by activation of glucocorticoid receptor and several agents manifested potential to activate or inhibit S100P promoter activity, this protein might become a therapy target and warrants further studies with respect to its prognostic, predictive and potentially therapeutic value.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Carcinoma Ductal de Mama/metabolismo , Núcleo Celular/metabolismo , Proteínas de Neoplasias/metabolismo , Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Proteínas de Ligação ao Cálcio/genética , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/terapia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Análise Multivariada , Proteínas de Neoplasias/genética , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , RNA Mensageiro/metabolismo , Fatores de Tempo , Regulação para Cima
14.
J Histochem Cytochem ; 61(5): 330-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23392733

RESUMO

BUBR1 (budding uninhibited by benzimidazole-related 1) represents the component of a controlling complex in mitosis. Defects in mitotic control complex result in chromosomal instability and, as a result, disturb the mitotic process. This study was aimed at examining the prognostic value linked to the expression of BUBR1 in a group of patients with breast cancer. We analyzed the expression of BUBR1 in 98 stage II breast cancer patients with a median follow-up of 15 years. Immunohistochemical reactions were performed using monoclonal antibodies against BUBR1. We also studied the prognostic value of BUBR1 mRNA expression using the Kaplan-Meier (KM) plotter, which assessed the effect of 22,277 genes on survival in 2422 breast cancer patients. A background database was established using gene expression data and survival information on 2422 patients downloaded from the Gene Expression Omnibus (GEO; Affymetrix HGU133A and HGU133+2 microarrays). The median relapse-free survival was 6.43 years. Univariate and multivariate analyses showed that higher expression of BUBR1 was typical for cases of shorter overall survival, disease-free time, and disease-specific survival. KM plotter analysis showed that elevated BUBR1 mRNA expression had a negative impact on patients' relapse-free, distant metastases-free, and overall survival. Elevated BUBR1 expression was associated with poor survival in early stage breast cancer patients.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Regulação Neoplásica da Expressão Gênica , Proteínas Serina-Treonina Quinases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sobrevida
15.
Anticancer Res ; 32(8): 3177-84, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22843890

RESUMO

BACKGROUND: Y-Box-Binding (YB1) protein represents a multifunctional protein, which plays a significant role in processes of proliferation, apoptosis and control of tumour cell response to toxic agents, including chemotherapy. The present study aimed at evaluating the prognostic significance of YB1 expression in breast cancer. MATERIALS AND METHODS: We analyzed nuclear and cytoplasmic expression of YB1 in 101 patients with stage II breast cancer, with 17 years of follow-up. Immunohistochemical reactions were performed on paraffin sections of primary tumours, using monoclonal antibodies against YB1. Results were tested for their correlation with clinical and pathological data. RESULTS: Patients with a pronounced expression of the nuclear form the YB1 protein demonstrated a highly significant shortening of disease-free survival, disease-specific survival and overall survival. The prognostic value of YB1 was also corroborated by multivariate analysis. CONCLUSION: We demonstrated that high nuclear expression of YB1 is associated with poor survival of patients with early-stage breast cancer.


Assuntos
Neoplasias da Mama/mortalidade , Núcleo Celular/metabolismo , Análise de Sobrevida , Proteína 1 de Ligação a Y-Box/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Prognóstico
16.
J Histochem Cytochem ; 60(7): 491-501, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22511598

RESUMO

Degradation of the extracellular matrix and basement membrane is a critical step in tumor progression. Matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP 2) act in a coordinated manner to form an integrated system involved in ovarian cancer (OC) progression. In this study, the authors describe the expression of TIMP-2 detected by immunohistochemistry in 6 OC cell lines and in 43 malignant epithelial ovarian tumors (in tumor and stromal compartments) in sections originating from primary laparotomies. No significant correlations between overall and progression-free survival and TIMP-2 expression in tumor compartment were observed. The analysis demonstrated a significant association between enhanced stromal expression of TIMP-2 and better clinical response to cisplatin- and paclitaxel-based chemotherapy. Increased expression of TIMP-2 in the stromal compartment and simultaneous overexpression in both stromal and tumor compartments strongly correlated with increased survival. No significant correlations were found in vitro between resistance to cisplatin, paclitaxel, or topotecan and the expression of TIMP-2 in the OC cell lines, suggesting stromal influences on tumor chemoresistance in the physiological environment. This study supports the concept of TIMP-2 expression in the stromal compartment of OC as a promising marker of prognosis and response to cisplatin- and paclitaxel-based chemotherapy in OC patients.


Assuntos
Biomarcadores Tumorais/imunologia , Carcinoma de Células Escamosas/diagnóstico , Compartimento Celular/imunologia , Neoplasias Ovarianas/diagnóstico , Células Estromais/imunologia , Inibidor Tecidual de Metaloproteinase-2/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/imunologia , Compartimento Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/imunologia , Valor Preditivo dos Testes , Prognóstico , Células Estromais/efeitos dos fármacos , Células Estromais/patologia , Inibidor Tecidual de Metaloproteinase-2/biossíntese , Células Tumorais Cultivadas
17.
Pathol Oncol Res ; 18(2): 331-42, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21986666

RESUMO

Nuclear expression of ABCC2 can be specific for lower differentiated cells and stem cells. The study aimed at examination of ABCC2 expression in breast cancers. The immunohistochemical analyses were performed on 70 samples of breast cancer. We have also studied prognostic value of the ABCC2 mRNA expression using the KM plotter which assessed the effect of 22,277 genes on survival in 1809 breast cancer patients. Immunohistochemical studies demonstrated that ABCC2 expression may be manifested in nuclear envelope of neoplastic cells (ABCC2n) as well as in their cell membrane and cytoplasm (ABCC2c). The univariate and multivariate analyses showed that higher expression of ABCC2n and ABCC2c was typical for cases of a shorter overall survival time. Higher ABBC2n expression was also typical for cases of a shorter disease-free survival and a shorter progression-free time. The KM plotter analysis of the prognostic value of ABCC2 mRNA expression showed that elevated ABCC2 expression was specific for cases of a shorter relapse-free survival only in the estrogen receptor-negative subgroup. The study demonstrated hat breast cancers manifest ABCC2 expression and that it is linked to a less favourable prognosis. Our results suggested that immunohistochemical tests represent a reliable way to detect prognostic value of ABCC2 expression, allowing to demonstrate differences related to subcellular localization of the protein. Cases with nuclear expression of ABCC2 manifested a more aggressive clinical course, which might reflect a less advanced differentiation of neplastic cells, resistance to the applied cytostatic drugs and tamoxifen.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Citoplasma/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Membrana Nuclear/metabolismo , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida
18.
Hepatogastroenterology ; 59(115): 724-6, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22094929

RESUMO

BACKGROUND/AIMS: To assess the incidence and risk of urinary complications after anterior rectal cancer resection with regard to the surgical device used for total mesorectal excision (TME). METHODOLOGY: During the years 2004-2009 we operated 374 rectal cancer patients with TME and the intent of autonomic nerves sparing intent. Seventeen patients underwent mesorectal dissection with ultrasound scalpel (US). They were compared to the control series of 35 cases selected from the patients for whom electrocautery was used. Selection was done in the manner to eliminate any other significant differences between groups. RESULTS: Intraoperative complications, postoperative mortality, anastomotic leakage and infectious complications did not occur. Urinary bladder disturbances developed in US group in 1 patient (6%) while in 12 patients (34%) in EC group (p<0.05). In US group the character of complication was transient stress incontinence with symptoms being significantly reduced during six postoperative months. In EC group two patients had dysuria, two nycturia, one had both. Stress incontinence occurred in six patients, complete incontinence requiring catheterization in one. CONCLUSIONS: When compared to EC, TME with US is related to lower risk of urinary complications and facilitates autonomic nerve preservation due to minimized thermal lateral tissue damage.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Dissecação/efeitos adversos , Eletrocoagulação/efeitos adversos , Sintomas do Trato Urinário Inferior/etiologia , Neoplasias Retais/cirurgia , Instrumentos Cirúrgicos/efeitos adversos , Procedimentos Cirúrgicos Ultrassônicos/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Procedimentos Cirúrgicos do Sistema Digestório/instrumentação , Dissecação/instrumentação , Disuria/etiologia , Eletrocoagulação/instrumentação , Desenho de Equipamento , Feminino , Humanos , Sintomas do Trato Urinário Inferior/terapia , Masculino , Pessoa de Meia-Idade , Polônia , Neoplasias Retais/patologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Ultrassônicos/instrumentação , Cateterismo Urinário , Incontinência Urinária/etiologia
19.
Ginekol Pol ; 83(9): 681-7, 2012 Sep.
Artigo em Polonês | MEDLINE | ID: mdl-23342897

RESUMO

UNLABELLED: Breast cancer resistance protein (BCRP, ABCG2) is a xenobiotic half-transporter protein. It is a member of the ATP-binding cassette protein family and functions as an energy-dependent efflux pump. BCRP is involved in multidrug resistance. The study aimed at examining BCRP expression in breast cancers and at defining a relationship between activity of this protein and clinical course of the cancer. MATERIALS AND METHODS: We analyzed the expression of BCRP in 101 stage II breast cancer patients. All the patients were diagnosed and treated at the Lower Silesia Oncology Centre (LSOC) between January 1993 and June 1994. After the treatment the patients remained under constant control at LSOC. Mean duration of the observation was 14.2 years (ranging between 9.1 and 16.5 years). Data related to relapse of the disease and deaths were obtained from medical documentation stored in LSOC. The immunohistochemical reactions were performed on paraffin sections of primary tumours, using monoclonal antibodies against BCRP. The intensity of immunohistochemical reactions with BCRP antibody was evaluated using the semi-quantitative IRS (ImmunoReactive Score) scale, which took into account the intensity of the colour reaction and percentage of positive cells. Results of the immunohistochemical reactions, pathological and of clinical observations were subjected to statistical analysis. Correlations between these factors and BCRP were analyzed using Spearman and Chi2 tests. In order to estimate the survival rate, we used Kaplan Meier statistics, log-rank tests and Cox proportional hazard regression. RESULTS: In our analysis we observed a positive correlation between the expression of the BCRP protein and grade of tumour advancement (r = 0.2 p = 0.03). We found also a negative correlation between the expression of BCRP and the estrogen (r = 0.24 p = 0.02) and progesteron (r = 0.28 p = 0.02) receptors. In a univariate analysis a significantly shorter disease free survival (DFS) and disease specific survival (DSS) was noted in patients with metastases to the lymph nodes (p = 0.003 and p = 0.0006), over the age of 50 years old ((p = 0.02 and p = 0.04) and clearly statistically significant in patients with a high expression of BCRP (p = 0.00044 and p = 0.00005). Overall survival (OS) was shorter in patients over the age of 50 (p = 0.01), with higher stage of the disease - IIB (p = 0.025), with metastases to the lymph nodes (p = 0.003) and also clearly statistically significant in patients with a high expression of BCRP (p = 0.00004). A multivariate analysis allowed to reveal that only higher expression of BCRP and metastases to lymph nodes were typical for cases of DFS (p = 0.,028 and p = 0.00015), DSS (p = 0.00052 and 0.000017) and OS (p = 0.0018 and p = 0.000007) time. CONCLUSIONS: We demonstrated that high BCRP expression level is associated with poor survival in early stage breast cancer patients.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Neoplasias da Mama/metabolismo , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Proteínas de Neoplasias/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Adulto , Idoso , Neoplasias da Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Polônia , Recidiva , Análise de Sobrevida
20.
Appl Immunohistochem Mol Morphol ; 19(6): 540-6, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21617523

RESUMO

The membrane cofactor protein, CD46 represents a complement inhibitor, which protects autologous cells from complement-mediated cytotoxicity. On tumor cells, CD46 may exhibit the potential to protect them from immune responses of the host. The present study aimed at evaluation of prognostic significance of CD46 expression in breast cancers. The analyses were performed on 70 samples of breast cancer. Immunohistochemical reactions were performed on paraffin sections of studied tumors using monoclonal antibodies directed against CD46. Results of the immunohistochemical reactions and of clinical observations were subjected to statistical analysis. Multivariate analysis showed that expression of CD46 and involvement of lymph nodes represent independent risk factors for disease-free survival and overall survival. Kaplan-Meier analysis showed that patients with tumors negative for CD46 have an increased progression-free time and overall survival time as compared with patients with the CD46-positive tumors. The study demonstrates that breast cancers manifest CD46 expression and that it is linked to a less favorable prognosis.


Assuntos
Antígenos de Neoplasias/metabolismo , Neoplasias da Mama/diagnóstico , Carcinoma/diagnóstico , Proteína Cofatora de Membrana/metabolismo , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/imunologia , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Carcinoma/imunologia , Carcinoma/patologia , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Evasão da Resposta Imune , Imuno-Histoquímica , Proteína Cofatora de Membrana/genética , Proteína Cofatora de Membrana/imunologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Regulação para Cima
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